Apparatus and methods for early stage peritonitis detection and for in vivo testing of bodily fluid

ABSTRACT

The invention provides, inter alia, automated medical methods and apparatus that test PD effluent in a flow path (e.g., with an APD system or CAPD setup) to detect, for example, the onset of peritonitis, based on optical characteristics of the effluent resolved at cellular scales of distance. For example, according to one aspect of the invention, an APD machine includes, in an effluent flow path, apparatus for early stage peritonitis detection comprising an illumination source and a detector. The source is arranged to illuminate peritoneal effluent in a chamber that forms part of the flow path, and the detector is arranged to detect illuminant scattered by the effluent. The detector detects that reflected or scattered illuminant at a cellular scale of resolution, e.g., on a scale such that separate cellular-sized biological (or other) components in the effluent can be distinguished from one another based on scattering events detected by the detector. Other aspects of the invention provide automated medical testing methods and apparatus that detect the onset of peritonitis and other bodily conditions by testing fluids in the body in vivo, e.g., the patient&#39;s peritoneum. Such apparatus and methods utilize a first fiber optic bundle to carry illuminant from a source of the type described above into a bodily organ or cavity, and a second fiber optic bundle to carry illuminant scattered by fluid in that organ or cavity to a detector as described above.

This application is a continuation in part of U.S. patent applicationSer. No. 11/880,656, filed Jul. 23, 2007, entitled “Early StagePeritonitis Detection Apparatus and Methods,” which claims the benefitof U.S. Provisional Patent Application Ser. No. 60/833,763, filed Jul.27, 2006, entitled “Early Stage Peritonitis Detection Apparatus andMethods,” the teachings of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The invention relates to apparatus and methods for medical diagnostictesting. It has application, inter alia, in detecting the onsite ofperitonitis, for example, during continuous ambulatory peritonealdialysis (CAPD) and automated peritoneal dialysis (APD) procedures.

Peritoneal dialysis (PD) is a medical procedure for removing toxins fromthe blood that takes advantage of the semi-permeable membranesurrounding the walls of the abdomen or peritoneal cavity. During a PDprocedure, a solution is introduced into the patient's abdomen, where itremains for up to several hours, removing blood toxins via osmotictransfer through that membrane. At completion of the procedure, thesolution is drained from the body along with the toxins. CAPD is themanual form of this procedure, requiring that the patient manually drainfresh PD solution into, and spent PD solution out from, the peritoneum.In APD, the entire procedure is handled by automated equipment.

Peritonitis is a common complication of both CAPD and APD. Often causedby introduction of bacteria (e.g., from the tubing, connectors and otherapparatus that make up the PD transfer set) to the peritoneum duringdialysis, this swelling of the peritoneum can cause vomiting, abdominaltenderness and a host of other symptoms. Although responsive toantibiotics, peritonitis can end a patient's ability to stay on APD andCAPD therapies. In extreme cases, it can be be fatal.

Standard tests for peritonitis, usually conducted on occurrence of acuteclinical symptoms, include the Gram stain procedure, performing a cellcount on the peritoneal fluid, culturing that fluid, and/or performing ablood culture. Largely, these tests can only be done in the lab, after apatient has presented with symptoms. By that time, the peritonitis maywell have set in, resulting in undue patient distress and potentiallynecessitating more extensive treatment.

More recently, reagent test strips have become available, making itpossible for physicians or patient's themselves to perform moreimmediate diagnosis. However, test strips have a limited time window ofutility and have generally not been successful in early stage detection.

CAPD and APD patients are typically counseled to maintain a keen eye foranother symptom of peritonitis: a turbid or cloudy effluent bag. Thiscan be late-developing, unfortunately, and is further compounded if thePD solution remains in the body for a long period before expulsion (asis the case, for example, during daytime dwells of APD patients).Detection of turbid effluent is further complicated in APD equipmentwith long drain lines, since patients may only see the effluent linesand not the effluent bag (where the turbidity is more readily apparent).Moreover, patients who are blind or have poor eyesight must rely onfriends, family and/or caregivers to inspect the spent PD fluid forturbidity.

The prior art suggests that such cloudiness might be detectedautomatically, e.g., within APD equipment, by detecting the overallamount of non-coherent, polychromatic light that passes through a vesselof PD effluent by use of a source of such light positioned on one sideof the vessel and a detector positioned at an opposing side.Implementations of this technique have generally not proven reliablebecause of poor signal-to-noise.

An object of the invention is to provide improved methods and apparatusfor medical diagnosis, testing and/or treatment in the home or lab.

A further object of the invention is to provide improved methods andapparatus for PD therapy.

A still further object of the invention is to provide improved methodsand apparatus for detecting the onset of peritonitis, e.g., inconnection with peritoneal dialysis.

Yet a still further object of the invention is to provide such methodsand apparatus as can be implemented at reasonable cost, yet, produceefficacious results.

SUMMARY OF THE INVENTION

The foregoing are among the objects attained by the invention whichprovides, in one aspect, automated medical testing methods and apparatusthat detect the onset of peritonitis from optical characteristics of PDeffluent resolved at cellular scales in the flow path.

For example, according to one aspect of the invention, an APD machineincludes, in an effluent flow path, apparatus for early stageperitonitis detection comprising an illumination source and a detector.The source is arranged to illuminate peritoneal effluent in a chamberthat forms part of the flow path, and the detector is arranged to detectilluminant scattered by the effluent. The detector detects thatscattered illuminant at a cellular scale of resolution, e.g., on a scalesuch that separate cellular-sized biological (or other) components inthe effluent can be distinguished from one another based on scatteringevents detected by the detector.

Related aspects of the invention provide apparatus as described above inwhich the detector is arranged such that separate white blood cells(WBCs) in the effluent can be distinguished from one another based onreflection and scattering (collectively, “scattering”) of illuminant.Apparatus with a detector so arranged can, by way of example, count suchWBCs from scattering and can, further, signal the onset of peritonitisif those counts change over time and/or vary from a baseline.

Further related aspects of the invention provide apparatus as describedabove in which the detector is arranged such that cellular-sizedbiological (or other) components of different types in the effluent canbe distinguished based on illuminant scattered by them. Related aspectsof the invention provide such apparatus in which the detector is soarranged as to permit WBCs in the effluent to be distinguished based onscattering from red blood cells (RBCs), fibrin and/or other components.

Other aspects of the invention provide apparatus as described abovewhich signal the onset of peritonitis based on variance, e.g., over timeand/or from a baseline, in counts of selected biological components inthe effluent. Related aspects of the invention provide such apparatus ascompute a trend of variance of those counts, e.g., with respect to WBCsin the effluent. Further related aspects of the invention provide suchapparatus which compute that trend as a slope of a curve of those countswith respect to time and that signals the onset of peritonitis when thatslope exceeds a selected amount.

Other related aspects of the invention provide such apparatus in whichthe detector counts scattering events—i.e., events in which illuminantis reflected and scattered from the effluent to the detector—based onintensity and/or location of the scattering event. In one such aspect ofthe invention, the detector comprises a pin diode that is configured tocount scattering events, e.g., based on the intensity of illuminantdetected from the effluent. An apparatus according to this aspect of theinvention can, for example, signal the onset of peritonitis when thenumber of counts of a certain intensity (or range of intensities, e.g.,which are based on cell size) varies, e.g., from a baseline and/or amongdrains of spent PD solution from the patient, and/or when a trend ofthat variance over time exceeds a selected amount.

In other such aspects, the detector comprises a charge-coupled device(CCD) that is arranged to image the chamber—that is, to recordscattering events based on both location and (cumulative) intensity.Further related aspects of the invention provide such apparatus in whichthe detector generates a histogram of one or more such images, countingscattering events (e.g., based on intensity). Still further relatedaspects of the invention provide such apparatus which generates ahistogram from multiple images taken, for example, during a drain ofspent PD solution from the patient. As above, apparatus according tothese aspects of the invention can, for example, signal the onset ofperitonitis when the number of counts of a certain intensity (or rangeof intensities) varies over time, e.g., from a baseline and/or amongsuccessive drains of PD effluent from the patient.

Other related aspects of the invention provide such apparatus which thehistograms are performed only with respect to selected scattering eventsrecorded in the images, e.g., scattering events of selected intensitiesand/or lengths. Apparatus accord to these aspects of the invention can,for example, signal the onset of peritonitis when the number of countsfrom scattering events likely caused by WBCs (and not, for example, RBCsor fibrin) vary over time from a baseline and/or among successive drainsof PD effluent from the patient.

Further aspects of the invention provide such apparatus in which theillumination source is a laser diode (or other source of coherentilluminant).

Related aspects of the invention provide such apparatus in which thedetector is arranged to detect side-scattering events, e.g., eventsdetectable within a field of view perpendicular to a ray of illuminantsourced by the laser diode.

Further related aspects of the invention provide such apparatus in whichilluminant sourced by the laser diode comprises a beam disposed—and,specifically, for example, centered—within a portion of the flow pathfrom which scattering events are counted by the detector.

Still further related aspects of the invention provide such apparatus inwhich illuminant sourced by the laser has a beam width selected based onsize characteristics of the biological (or other) components from whichscattering events are to be counted. Further related aspects of theinvention provide such methods in which the beam width has a diameter ofabout 1.5 times a size of components, e.g., WBCs. Yet still otheraspects of the invention provide such apparatus in which the beam widthhas any of a circular and gaussian cross-section, or other beam sizeand/or shape.

Further aspects of the invention provide such apparatus in which thedetector comprises a lens arranged to resolve illuminant scattered fromcomponents of the effluent at a cellular scale of distances. Relatedaspects of the invention provide such apparatus in which the lens isarranged to provide a depth of field encompassing a substantive portionof the flow path within the detector field of view, e.g., a depth offield that encompasses a flow chamber from which scattering events aredetected.

Further aspects of the invention provide apparatus as described above inwhich the aforementioned chamber induces lamellar flow in the effluent.Such a chamber can comprise, for example, an optically clear portionhaving a central portion with inner walls defining a generally cuboid orrectangular parallelepiped region.

The central portion can, according to related aspects of the invention,be coupled with a flow inlet port via a portion of the chamber havinginner walls generally defining a pyramidal frustum. Likewise, thecentral portion can, according to still further related aspects of theinvention, be coupled with a flow outlet port via a portion of thechamber having inner walls that also generally define a pyramidalfrustum.

Still further aspects of the invention provide apparatus as describedabove wherein the chamber comprises a deflector disposed in the flowpath. The deflector can increase turbulence of effluent flowing in thechamber, increasing the Reynold's number of the fluid, e.g., to a valueof about 100 or greater and, more preferably, of about 250 or greater.In these and other aspects of the invention, turbulence introduced intothe flow as a result of the deflector facilitates cleaning its innerwalls—particularly, for example, removing from them white blood cells,red blood cells and other components of the effluent.

Other aspects of the invention provide automated medical testing methodsand apparatus paralleling those described above that detect the onset ofperitonitis and other conditions by testing peritoneal fluid in vivo,i.e., in the patient's peritoneum. According to one aspect of theinvention, such an apparatus includes an illumination source and adetector as described above, both disposed external to the patient. Afirst fiber optic bundle carries illuminant from the source into theperitoneum. A second fiber optic bundle carries illuminant scattered byperitoneal fluid in the peritoneum to the detector.

Related aspects of the invention provide apparatus as described above,wherein distal ends of the first and second fiber optic bundles areconfigured so that the latter detects and transmits to the detectorreflected and/or scattered (collectively, “scattered”) illuminant at acellular scale of resolution, e.g., on a scale such that separatecellular-sized biological (or other) components in the peritoneal fluidcan be distinguished from one another.

In other related aspects of the invention, one or more of the fiberoptic bundles are routed from the apparatus to the patient's peritoneumvia a catheter. This can be, for example, a catheter that forms part ofan APD machine, CAPD system, or other equipment with which the apparatusis used. In related aspects, the bundles can enter the catheter via ay-connector, direct insertion into the wall of the catheter, orotherwise.

In still other related aspects of the invention, illuminant generated bythe source (e.g., a laser diode) is shaped by lens or columnator fortransfer via the first optic bundle to the peritoneum. Likewise, afurther lens or columnator can be provided at the distal end of thefirst bundle to shape the illuminant in the peritoneum, e.g., to achievea gaussian or circular cross-section. In further related aspects of theinvention, a beam of illuminant emanating from the distal end of thefirst bundle can be aimed to pass through peritoneum so as to illuminateperitoneal fluid therein for purposes of evoking scattering frombiological (and other) components in that fluid.

In yet other related aspects of the invention, the second fiber opticbundle is arranged to capture—and, thereby, to transmit to thedetector—illuminant side-scattered by peritoneal fluid within theperitoneum. In related aspects of the invention, that bundle is arrangedto capture and transmit to the detector illuminant back-scattered,forward-scattered, and/or side-scattered in the peritoneum.

Other aspects of the invention provide apparatus as described abovewhich signal the onset of peritonitis or other conditions via a remotelydisposed interface. In these regards, the apparatus and the remotelydisposed interface can be coupled for communication via a wireless link,such as a Bluetooth® connection. Other aspects provide for such couplingvia a wired link or a combination of wired and wireless links.

The remote interface can, according to still other aspects of theinvention, receive signaling from the aforementioned apparatus anddisplay it, e.g., via liquid crystal display, light-emitting diodes, orother indicators, to the patient, health care provider, or others.Furthermore, the remote interface can control the apparatus, e.g., inresponse to input from the patient, health care provider or others. Thiscan include activating the apparatus, instigating coupling/decoupling ofthe interface and apparatus, specifying operational modes for theapparatus or otherwise.

In still other aspects of the invention, the remote interface is sizedand configured to be slipped onto/into a pocket or “worn” by thepatient, health care provider, or otherwise.

Still other aspects of the invention provide apparatus as describedabove that detects and measures an index of refraction of peritonealfluid in the patient's peritoneum.

Other aspects of the invention provide apparatus as described above foruse in connection with CAPD procedures.

Still other aspects of the invention provide such apparatus for use indetecting the onset of peritonitis in fluid flows establishedindependent of APD and/or CAPD equipment in which the PD fluid iscollected. Such apparatus has application, for example, in testing bags(or other collections) of spent PD effluent, e.g., as they are beingemptied for disposal or for further testing.

Yet still other aspects of the invention provide PD kits that include,in addition to conventional components (such as tubing, clamps,sterilization wipes, and so forth), a test apparatus as described above.

Still yet other aspects of the invention provide methods of testing PDeffluent for the onset of peritonitis paralleling the operationsdescribed above.

Yet still other aspects of the invention provide apparatus as describedabove for in vivo testing of bodily fluids including and other thanperitoneal fluid.

Yet still other aspects of the invention provide apparatus and methodsas described above for use in detecting characteristics of dialysate andother fluids contained in and/or from bodily organs and cavities invitro, in vivo and otherwise, including characteristics such as indexesof refraction, the presence of blood (RBCs), bubbles and otherundesirable byproducts of CAPD, APD, and so forth. A related aspect ofthe invention is to provide such apparatus and methods for use inhemodialysis and other medical procedures

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the invention may be attained byreference to the drawings, in which:

FIGS. 1A-1E depict an automated peritoneal dialysis (APD) treatmentsystem according to one practice of the invention and of the type withwhich the invention can be practiced;

FIGS. 2A-2C depict a continuous ambulatory peritoneal dialysis (CAPD)treatment system according to one practice of the invention and of thetype with which the invention can be practiced;

FIGS. 3A-3B depict apparatus for testing PD effluent according to onepractice of the invention;

FIG. 4 depicts an image of the type generated by a charge coupled devicein an apparatus according to one practice of the invention;

FIGS. 5A-5C depict histograms of the type generated from imagesgenerated by charge coupled devices used in practice of the invention;

FIGS. 6A-6C show an alternate effluent flow chamber for use in a systemaccording to the invention;

FIGS. 7A-7B depict APD and CAPD systems according to the inventionutilizing apparatus for in vivo testing of peritoneal fluid according tothe invention; and

FIG. 8 depicts further details of the in vivo testing apparatus of FIG.7.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENT

FIG. 1A depicts an automated peritoneal dialysis (APD) treatment system10 according to one practice of the invention and of the type with whichthe invention can be practiced. The system 10 includes a cycler 12 orother apparatus to facilitate introducing fresh peritoneal dialysis (PD)solution into, and removing spent PD solution from, the peritoneum 14 ofa patient 16.

The system 10 includes a PD solution supply chamber 18, a heatingchamber 20, a weigh chamber 22, and a disposal chamber 24, allconstructed an operated in the conventional manner known in the art(albeit as adapted for inclusion of PD effluent test apparatus asdiscussed elsewhere herein). Thus, PD supply chamber 18 holds a supplyof fresh PD solution for delivery to the patient 16; heating chamber 20brings the fresh PD solution to an appropriate temperature for deliveryto the peritoneum; weigh chamber 22 hold spent PD solution expelled fromthe peritoneum, e.g., for weighing; and, disposal chamber 24 holds spentPD solution for disposal.

Pump 26 operates under control of a micro-controller (not shown) to movesolution between the chambers 18-24 in the conventional manner, e.g., asillustrated in FIGS. 1B-1E. Thus, for example, as shown in FIG. 1B, pump26 moves fresh PD solution from supply chamber 18 to heating chamber 20so that the latter can bring that solution to temperature, prior to itsintroduction into the patient's peritoneum 14 via catheter 19. Once thedesired temperature is achieved and treatment is to begin, the pump 26opens a valve 28, allowing the heated, fresh PD solution to flow viagravity-assist into the peritoneum 14. See, FIG. 1C.

Per FIG. 1D, once the PD has dwelled for the desired period of time inthe peritoneum 14, pump 26 opens valve 28 so that the spent PD solutioncan flow into chamber 22 for weighing (e.g., to insure that sufficientsolution has be removed from the peritoneum 14), as per convention inthe art. Pump 26 then moves the spent effluent from the weigh chamber 22to the disposal chamber 24 for collection prior to disposal by thepatient, health care worker, or otherwise. See, FIG. 1D.

The conventional aspects of system 10 shown and described here aremerely by way of example. It will be appreciated that apparatus fortesting PD effluent (as discussed elsewhere herein) may be used inconnection with APD equipment of other configurations and modes ofoperation than those shown in FIGS. 1A-1E and described above.

FIG. 2A depicts a continuous peritoneal dialysis (CAPD) treatment system30 according to one practice of the invention and of the type with whichthe invention can be practiced. The system 30 includes a fresh PDsolution supply bag 32, a spent PD solution bag 34, and a y-connector 36for coupling those bags to peritoneal transfer set 38. The system 30 isconstructed and operated in the conventional manner known in the art(albeit as adapted for inclusion of PD effluent test apparatus asdiscussed elsewhere herein). Thus, for example, the patient connectsbags 32, 34 to the y-connector 36, as shown in FIG. 2B, for a briefsterilizing flush of the connector 36. Then, as further shown in thatdrawing, the patient configures the connector 36 to permit fresh PDsolution to flow, under gravity assist, from bag 32 into the peritoneum.Once the PD solution has dwelled for the desired period, the patientreconfigures the connector 36 to permit the spent PD solution to drainto bag 34 for disposal. See, FIG. 2C.

The conventional aspects of system 30 shown and described here aremerely by way of example. It will be appreciated that apparatus fortesting PD effluent (as discussed elsewhere herein) may be used inconnection with CAPD equipment of other configurations (e.g., withstraight transfer tubing sets) and modes of operation than those shownin FIGS. 2A-2C and described above.

FIG. 3A depicts an APD cycler 40 that is constructed and operated in themanner of cycler 12 (FIG. 1), albeit including apparatus 42 according tothe invention for testing PD effluent (i.e., PD solution drained fromthe peritoneum) in a flow path of cycler 40 and/or other APD system orcomponents of which it is a part. The cycler 40 (with test apparatus 42)can be used in place of cycler 12 in the system 10 (FIG. 1), as well asin other APD treatment systems. Likewise, the test apparatus 42 can becoupled into the effluent flow path (i.e., drain lines) of the system 30(FIG. 2), as graphically depicted in inset FIG. 3B, as well as in otherCAPD systems. Moreover, the apparatus can be combined with kits for APDand CAPD procedures (e.g., kits that include tubing, clamps,sterilization wipes and so forth). Still further, the apparatus 42 canbe coupled into fluid flow paths of laboratory, doctor's office,hospital or home test equipment and it can be sold with kits for suchtesting (e.g., kits that include PD effluent sample phials, drop boxes,labeling and so forth). For convenience, operation of test apparatus 42will be described with respect to cycler 40 of FIG. 3A, though, it willbe appreciated that apparatus 42 can be configured and operatedsimilarly in the aforementioned and other environments in which it isused.

By way of overview, illustrated apparatus 42 tests PD effluent in a flowpath—here, the path from peritoneum 14 to disposal chamber 24—for theonset of peritonitis and/or other conditions (e.g., the presence ofblood and/or bubbles). To this end, that apparatus includes anillumination source 44 and a detector 46. The source 44 is arranged toilluminate peritoneal effluent in a chamber 48 that forms part of theflow path, and the detector 46 is arranged to detect illuminantscattered by that effluent, e.g., in a direction normal to theilluminant beam.

The source 44 and detector 46 are configured so that the detectordetects reflected and/or scattered (collectively, “scattered”)illuminant at a cellular scale of resolution, e.g., on a scale such thatseparate cellular-sized biological (or other) components in the effluentcan be distinguished from one another. In applications such as those towhich the illustrated embodiment is directed, i.e., early detection ofthe onset of peritonitis, this permits separate white blood cells (WBCs)in the effluent to be distinguished from one another (as well as fromred blood cells, fibrin and other components of the effluent) so thatthey can be counted and so that the rate of change of those counts canbe measured for purposes of detecting and signaling the onset ofperitonitis. In other embodiments, this permits red blood cells (orother components, such as bubbles) in the effluent to be distinguishedfrom one another (as well as from WBCs, fibrin, etc.) and counted; andso forth.

As noted, detector 46 is configured to detect illuminant scattered fromthe chamber 48 at a cellular scale of resolution, e.g., on a scale suchthat separate cellular-sized components in the effluent can bedistinguished from one another. As further noted, in the illustratedembodiment, this permits separate WBCs 54 in the effluent to bedistinguished from one another (as well as from red blood cells 56,fibrin 58 and other components of the effluent) so that they can becounted and so that the rate of change of those counts can be measuredfor purposes of detecting and signaling the onset of peritonitis. Inother embodiments, this permits other components—such as RBCs 56, fibrin58, etc.—to be detected in the effluent for purposes signaling otherother conditions.

The illumination source of the illustrated embodiment comprises alow-power laser diode generating a monochromatic collimated beam. Here,the wavelength is selected at 630 nm to coincide with an opticalsensitivity of detector 46 and for suitability in reflection andscattering (collectively, as above, “scattering”) from at least selectedcomponents (e.g., white blood cells) in the effluent. Other embodimentsmay utilize lasers of other wavelengths, monochromatic or otherwise,selected in accord with foregoing or other criterion, e.g., 830 nm and780 nm lasers, to name but a few, as well as other illumination sources,monochromatic, polychromatic, coherent and/or otherwise.

The collimated beam generated by laser diode 44 of the illustratedembodiment is optionally shaped by lens or columnator 50 to result in abeam 52 of gaussian or circular cross-section, though beams of othershapes may be used in other embodiments.

Lens 52 shapes the beam to optimize scattering from at least selectedcomponents in the effluent. In the illustrated embodiment, this meanssizing the beam at 1×−2× and, preferably, about 1.5× the average size ofthe effluent components to be preferentially be detected—here, WBCs.Given an average size of 12-15 μm for neutrophils and eosinophils, 8-10μm for lymphocytes, and 16-20 μm for monocytes, beam 52 of theillustrated embodiment is accordingly sized between 10-40 μm and,preferably, 15-25 μm and, still more preferably, about 20 μm. Thisoptimizes the apparatus 42 for preferential detection of WBCs over, forexample, red blood cells 56, fibrin 58 and other components of the PDeffluent. Other embodiments may use other beam sizes, e.g., for reasonof preferential detection of other effluent components or otherwise.

The beam 52 of the illustrated embodiment is aimed to pass throughchamber 48 in order to illuminate the effluent therein for purposes ofevoking scattering from biological (and other) components in that fluid.Although in the illustrated embodiment, the beam is aimed to passthrough a center of the chamber 48, as shown, in other embodiments thebeam 52 may be directed otherwise.

Turning back to FIG. 3A, detector 46 detects and counts scatteringevents—i.e., events in which illuminant is scattered from the effluentin the chamber 48 to the detector 46—based on the intensity and/orlocation of those events. In the illustrated embodiment, the detector 46is, particularly, arranged to detect side-scattering, e.g., eventswithin a field of view 64 centered on an axis 66 that is normal to thebeam 52, as shown. In other embodiments, the detector may be arranged todetect other scattering events, e.g., back-scattering,forward-scattering, side-scattering at angles β other than normal. Thus,while in the illustrated embodiment, β is substantially 90°, moregenerally, β is in the range 30°-150°; more preferably, between,60°-120°; still more preferably, between 80°-100°; and, still morepreferably, substantially 90°, as illustrated.

In some embodiments, the detector 46 employs a single-cell (orfew-celled) photo diode, i.e., pin-diode 68, for purposes of detectingand signaling the occurrence of such scattering events. A lens 70facilitates focusing the diode so that it detects those events at acellular scale of resolution, e.g., on a scale such that separatecellular-sized biological (or other) components in the effluent can bedistinguished (based on such scattering) from one another. In theillustrated embodiment, lens 70 is selected and arranged (vis-a-vischamber 48 and diode 68) to preferentially focus WBCs, though, in otherembodiments, the lens 70 may be focused otherwise. The lens 70 isfurther selected and arranged for a desired depth of focus within thefield of view 64, e.g., in the illustrated embodiment, a depth of focusmatching the depth of compartment 48, or a substantial portion thereof.The chamber 48 is configured to match the laser beam size and shape,e.g., so as to minimize or wholly avoid reflections (or scattering) ofthe beam 52 off the inner walls of the chamber itself

The laser diode 68 is selected and/or otherwise configured (e.g.,through use of appropriate circuitry) to detect scattering from selectedcomponents of the effluent—here, preferentially, WBCs, though, in otherembodiments, RBCs, fibrin, bubbles other components of the effluent.Regardless, such selection and/or configuration can be performedempirically (e.g., by testing scattering detected from an effluent ofknown composition) or otherwise.

Scattering events detected and signaled by the diode 60 are routed to amicroprocessor 62 (or other suitable element) for analysis. In theillustrated embodiment, this comprises counting events signaled overtime and generating an alert, e.g., when the number of counts of acertain intensity (or range of intensities) varies, e.g., (i) from abaseline established for patient 16, (ii) among successive drains ofspent PD solution from that patient 16, and/or (iii) when a trend ofthat variance over time—and, more particularly, a rate of change ofcounts over time (i.e., a “critical slope”)—exceeds a selected amount.Such an alert can be in the form of a visible and/or audible signal tothe patient 16, health-care worker, or otherwise; a hardware or otherinterrupt to system 12 of which test apparatus 42 forms a part; asoftware function call to such system; or otherwise.

Other embodiments of the invention employ a charge-coupled device (CCD),in place of pin-diode 68, for purposes of detecting and signaling theoccurrence of scattering events. As above, lens 70 facilitates focusingthe CCD (and obtaining a desired depth of focus) so that it detectsthose events at a cellular scale of resolution and, in the illustratedembodiment, so that it preferentially focuses WBCs—though, in otherembodiments, the lens 70 may be focused otherwise. In the discussionthat follows, elemental designation 68 is used for the CCD, as it wasfor the pin-diode, since the CCD is disposed in the same functionalplace in apparatus 42.

As with the pin-diode, the CCD 68 is selected and/or otherwiseconfigured to facilitate detection of scattering from selectedcomponents of the effluent (again, here, preferentially, WBCs). In thisregard, the CCD 68 images the illuminated chamber 48, recording both thepositions and intensities of scattering events (again, at a cellularscale of resolution) so that at least selected components (e.g., WBCs)in the effluent can be distinguished from one another and from othercomponents of the effluent.

FIG. 4 depicts such an image—here, generated from a simulated effluentincorporating, in lieu of WBCs, 80 glass beads (sized between 10-30microns) per μL.

Images generated by the CCD are routed to the microprocessor 62 (orother suitable element) for analysis. In the illustrated embodiment,this comprises taking a histogram of each image—or, more preferably,from multiple such images generated during drainage of spent PD solutionfollowing a single PD treatment session—with binning that is based onintensity. Depending on the number of counts in selected one(s) of thehistogram bins, the microprocessor 62 can generate an alert, e.g., asdiscussed below.

FIGS. 5A-5C depict such histograms—here, generated from a simulatedeffluent as described above with, respectively, 40 (FIG. 5A), 80 (FIG.5B) and zero (FIG. 5C), glass beads per μL.

In the illustrated embodiment, it generates that alert, e.g., when thenumber of counts of a certain intensity (or range of intensities)varies, e.g., (i) from a baseline established for patient 16, (ii) amongsuccessive drains of spent PD solution from that patient 16, and/or(iii) when a trend of that variance over time (i.e., from PD treatmentsession to session)—and, more particularly, a rate of change of countsover time (or “critical slope”)—exceeds a selected amount. Again, suchan alert can be in the form of a visible and/or audible signal to thepatient 16, health-care worker, or otherwise; a hardware or otherinterrupt to system 12 of which test apparatus 42 forms a part; asoftware function call to such system; or otherwise.

As will be appreciated, an advantage of taking histograms from multipleCCD images is that it tends to emphasize intensity counts in thecritical range. This improves the signal-to-noise ratio and, thereby,increases the efficacy of detection (e.g., of peritonitis or otherconditions reflected by the effluent). In embodiments of the inventionusing this approach, the CCD 68 can be controlled (e.g., by themicroprocessor 62 or otherwise) to acquire those multiple images duringPD solution drainage by successively entering “acquisition” and “read”modes: the former, for acquiring images of the illuminated chamber 48;and the latter for reading those images to the microprocessor.

In other embodiments of the invention, the microprocessor can performimage pre-processing prior to taking the histograms. Thus, for example,it can eliminate pixel values representing scattering from effluentcomponents that are too long (e.g., fibrin) or too short (e.g.,RBCs)—both, by way of example, with respect to embodiments intended tocount WBCs for purposes of peritonitis detection. Further suchpreprocessing may be selected depending upon the specifics of theapplication to which the invention is applied.

Self-Cleaning Chamber

FIGS. 6A-6C depict a chamber 82 for use with apparatus 42. This is analternate to the chamber 48 shown in FIG. 3A and discussed above. Thus,as with chamber 48, chamber 82 forms part of the flow path forperitoneal effluent and can be arranged so that effluent flowing throughit can be illuminated by source 44 and detected by detector 46, all asdescribed above with respect to chamber 48 in view of the discussionbelow.

FIGS. 6A and 6B depict front and side views, respectively, of chamber82. FIG. 6C illustrates a configuration of a system according toinvention showing chamber 82 in combination with source 44 and detector46.

Referring to FIGS. 6A and 6B, chamber 82 includes a fluid inlet port 84and outlet port 86 for coupling into the effluent flow path of cycler40, system 30, or other APD or CAPD systems as described above, witheffluent fluid flow in the direction of arrows 88, 90 from theperitoneum (or “transfer side”) to the disposal chamber (“or drainside”). In the illustrated embodiment, the ports 84, 86 are dimensionedfor attachment of tubing otherwise defining such effluent flow path insuch APD or CAPD systems; though, it will be appreciated that the sizingand configuration of the ports may vary in other embodiments.

Chamber 82 defines a region in which effluent flowing in port 84 passesprior to exit via port 86. The chamber 82 of the illustrated embodimentincludes a central portion 82A with inner walls (indicated by dashedlines) defining a fluid flow region generally characterized as arectangular parallelepiped, or cuboid, with dimensions l (length), w(width), and d (depth).

In the illustrated embodiment, the length l and width w are generally ofthe same size, and both are greater in size than the depth d; however,other embodiments may vary in these regards. In one embodiment of theinvention, l and w are both less than or equal to about 5″ and,preferably, less than or equal to about 3″ and, still more preferably,less than or equal to about 1″, while d is less than or equal to about1″ and, more preferably, less than or equal to about ½″ and, still morepreferably, less than or equal to about ¼″. Thus, in one particularembodiment, l and w are about 1″ and d is about ¼″.

The central portion 82A is coupled with port 84, on the inlet side, viaa proximal portion 82B having inner walls (dashed lines) with a shapegenerally characterized as a pyramidal frustum; and, on the outlet side,via distal portion 82C having inner walls (dashed lines) also with ashape generally characterized as a pyramidal frustum. The dimensions ofthe frustum defined by the inner walls of portion 82B at the proximalend (i.e., closer to the inlet) substantially match the inner diameterof the port 84 and, at the distal end (i.e., close to the outlet),substantially match the dimensions of cuboid defined by the innerdiameter of portion 82A. Likewise, the dimensions of the frustum definedby the inner walls of portion 82C at the distal end (i.e., closer to theoutlet) substantially match the inner diameter of the port 86 and, atthe proximal end (i.e., close to the inlet), substantially match thedimensions of cuboid defined by the inner diameter of portion 82A.

Central portion 82A of the illustrated embodiment is optically clear,permitting illumination of peritoneal effluent in chamber 82 by source44 and detection of illuminant scattered thereby by detector 46, asdiscussed above. To these ends, at least central portion 82A can befabricated from molded plastics such as acrylic, polycarbonate and/orpolystyrene, which have optical transmission of 450 nm-890 nm (withmaximum optical loss of around three percent) and are therefore suitablefor use with a source 44 operating at a wavelength of 630 nm (+/−20 nm).Of course, other plastics or materials (such as glass, ceramics, etc.)that are optically transparent in the wavelengths discussed herein andearlier may be used as well or in addition.

In the illustrated embodiment, the index of refraction of the plastic orother material from which central portion 82A is fabricated (within theconstraints discussed above) has little significant impact onillumination of peritoneal effluent in chamber 82 by source 44 anddetection of illuminant scattered thereby by detector 46. However, inother embodiments, e.g., where a portion of region 82A serves as a lens(intentionally or otherwise), the index of refection of that plastic orother material may be more significant.

Likewise, in the illustrated embodiment, the dispersion factor of theplastic or other material from which central portion 82A is fabricated(again, within the constraints discussed above) has little significantimpact on illumination of peritoneal effluent in chamber 82 by source 44and detection of illuminant scattered thereby by detector 46. This isparticularly true where (i) the beam 52 transits the walls of centralportion 82 at an angle L that is substantially normal to the surfacesthereof, (ii) the beam is collimated, and (iii) the beam has a diameter(and is positioned) so that no portion of it comes in contact with thesides of the central portion 82A—other than the points of transit.However, in other embodiments, where the beam transits the walls of thecentral at an angle Ω other than substantially 90° central portion 82Acan be fabricated from materials with lesser dispersion factors.

Although portions 82B, 82C of compartment 82 can be fabricated from thesame plastic or other material as portion 82A, proximal and distalportions 82B, 82C need not be optically clear and, hence, can befabricated from other materials, as well.

A deflector 94 is disposed at the distal end of the interior chamber 82,as shown. In the illustrated embodiment, it comprises an arc- orhemispherically-shaped member positioned in a central region of theeffluent flow path downstream of a region illuminated by beam 52. Thus,for example, the deflector may be disposed at the distal end of chamber82, yet, substantially centered vis-a-vis the x- and z-axes 96 (or, putanother way, vis-a-vis the width w and depth d dimensions).

The deflector 94, which may be coupled or integral to the distal portion82, has a rounded portion (shown as a thick, dark, curved region in thedrawing) that protrudes into the distal end of the central portion 82A,as shown. Deflectors of other shapes suitable for breaking up theeffluent flow (e.g., from lamellar to turbulent) in the manner discussedbelow may be used, as well or in addition to deflector 94 shown here.Deflector 84 may be fabricated from the same plastic or other materialsas portions 82A, 82B and/or 82C, though it may be fabricated from othermaterials as well. In some embodiments, deflector 84 bears a coating ofteflon or other substance that resists adherence of biological and othermaterials in the effluent flow.

As a consequence of the configuration of its inner waits, chamber 82induces lamellar flow in effluent at the proximal end of the centralportion 82A. The deflector 94 provides a transition in that flow at thedistal end of the central portion 82A, as well as in outlet (or distal)portion 82C, from lamellar to turbulent by breaking up the boundarylayer, which causes the Reynold's Number to increase. When the Reynold'snumber reaches 100, eddies start to form in the effluent. Those eddiesincrease as the Reynold's number gets larger. The eddies help clean theinner walls of the chamber 82—particularly, for example, at the distalend of the central portion 82A, as well as in distal portion82C—preventing white blood cells, red blood cells, and other componentsof the effluent from adhering to those inner walls and/or removing thosethat have already adhered. Thus, in one embodiment of the invention, thedeflector is arranged to effect a flow of effluent having a Reynold'sNumber that is about 100 or higher and, more preferably, about 250 orhigher.

In Vivo Testing

FIG. 7A depicts an APD cycler 40 that is constructed and operated in themanner of cycler 12 (FIG. 1), albeit including apparatus 100 a accordingto the invention for detection of peritonitis by testing peritonealfluid in vivo, i.e., in the patient's peritoneum. The cycler 40 (withtest apparatus 100 a) can be used in place of cycler 12 in the system 10(FIG. 1), as well as in other APD treatment systems. Likewise, the testapparatus 100 a can be used with system 30 (FIG. 2), as graphicallydepicted in inset FIG. 7B, as well as in other CAPD systems. Moreover,the apparatus 100 a can be utilized as a stand-alone test apparatus(e.g., for testing fluids in a patient's body) and/or it can be combinedwith kits for APD, CAPD or other medical procedures. Still further, theapparatus 100 a can be used, alone or in combination with the foregoing,in laboratory, doctor's office, hospital or home test equipment. Forconvenience, operation of test apparatus 100 a will be described withrespect to cycler 40 of FIG. 3A, though, it will be appreciated thatapparatus 100 a can be configured and operated similarly in theaforementioned and other environments in which it is used.

Illustrated apparatus 10 a generally operates in the manner of testapparatus 42, discussed above, albeit testing peritoneal fluid in vivofor the onset of peritonitis and/or other conditions (e.g., the presenceof blood and/or bubbles)—in the abdomen and, more particularly, in theperitoneum 14 of the patient 16—rather than in chamber 48. In addition,apparatus 100 a of the illustrated embodiment provides for measurementof characteristics of the peritoneal fluid, e.g., its index ofrefraction.

When used with APD and CAPD systems (e.g., as shown in FIGS. 7A-7B),this testing is typically conducted during PD treatment—i.e., at a timewhen the peritoneum is filled with a mix of bodily fluids (e.g., creatinand urea) and PD solution. The apparatus 100 a may also be used pre- orpost-treatment to test peritoneal fluid that comprises substantiallyonly bodily fluids. In light of the latter, it will be appreciated thatthe term “peritoneal fluid” as used herein in regard to the content ofthe peritoneum refers to any combination of fluids (e.g., bodily fluids,PD solution, or a mix thereof), unless otherwise evident from context.

To these ends, apparatus 100 a utilizes a first fiber optic bundle 102to carry illuminant down catheter 19 from illumination source 44(external to the patient) into the peritoneum 14. A second fiber opticbundle 104 carries illuminant scattered by peritoneal fluid in theperitoneum, e.g., in a direction normal to the illuminant beam, back upthe catheter 19 to the detector 46 (also external to the patient). Inembodiments where apparatus 100 a is used with APD and CAPD systems, thebundles may be routed through transfer sets 38, as well.

Referring to FIG. 8, the distal ends of bundle 102 and bundle 104 aresecured in catheter tip 105 so that the latter captures and transmits todetector 46 reflected and/or scattered (collectively, “scattered”)illuminant—preferably, at a cellular scale of resolution, e.g., on ascale such that separate cellular-sized biological (or other) componentsin the peritoneal fluid can be distinguished from one another. As notedabove, in applications such as those to which the illustrated embodimentis directed, i.e., early detection of the onset of peritonitis, thispermits separate white blood cells (WBCs) in the peritoneal fluid to bedistinguished from one another (as well as from red blood cells, fibrinand other components of the fluid) so that they can be counted and sothat the rate of change of those counts can be measured for purposes ofdetecting and signaling the onset of peritonitis. In other embodiments,this permits red blood cells (or other components, such as bubbles) inthe fluid to be distinguished from one another (as well as from WBCs,fibrin, etc.) and counted, and so forth.

Tip 105 may be constructed of plastic, ceramic, metal or other materials(or combination thereof) suitable for use in medical application forsecuring the bundles 102, 104. In the illustrated embodiment, itcomprises a hood-shaped structure with a hollow central region in whichthe distal ends of bundles 102, 104 are disposed (as shown) and throughwhich peritoneal fluids, as well as fresh and spent dialysaic, mayfreely pass. An open “face” region of the hood-shaped structure andapertures 107 at its distal end (or “top”) further facilitates suchpassage of fluids. In addition, the open face and apertures help insurethat distal tips 102, 104 are exposed to a representative mix of fluidsfrom the peritoneum. Those skilled in the art will of course appreciatethat other structures and/or arrangements may be used in addition to, orin place of, tip 105.

Fiber optic bundles 102, 104 can be routed from apparatus 102 toperitoneum 14 through catheter 19 in the manner shown, e.g., enteringthe catheter 19 via an integral catheter branch 19 a. Alternatively, thebundles 102, 104 can enter the catheter via a y-connector, via directinsertion into the wall of the catheter 19, or via other techniquesknown in the art for the routing of fiber optic bundles or other suchstructures through catheters into a patient's body. The bundles 102, 104are comprised of conventional fiber optic fibers suitable for use inmedical applications. Each bundle, which is sized to that it (and itspartner) may pass through the catheter 19 without unduly impeding theflow of dialysate therethrough, comprise between one and hundreds, ormore, of fibers, depending on individual fiber size.

As above, illumination source 44 of apparatus 100 a comprises alow-power laser diode generating a monochromatic collimated beam. Thewavelength is selected at 630 nm to coincide with an optical sensitivityof detector 46 and for suitability in reflection and scattering(collectively, as above, “scattering”) from at least selected components(e.g., white blood cells) in the peritoneal fluid. As noted earlier,other embodiments may utilize lasers of other wavelengths, monochromaticor otherwise, selected in accord with foregoing or other criterion,e.g., 830 nm and 780 nm lasers, to name but a few, as well as otherillumination sources, monochromatic, polychromatic, coherent and/orotherwise. Source 44 can be powered and otherwise driven by illustrateddrive circuitry 108 in the conventional manner of laser diode drivecircuitry known in the art—as adapted in accord with the teachingshereof.

As above, the collimated beam generated by laser diode 44 of apparatus100 a can be shaped by lens or columnator 50 a for transfer down bundle102 to the peritoneum 14. A further lens or columnator 50 b can beprovided at the distal end of the bundle 102 to shape the laser beam 52in peritoneal cavity 14 in a gaussian or circular cross-section, thoughbeams of other shapes may be used in other embodiments.

As above, lens 50 b shapes the beam 52 to optimize scattering from atleast selected components in the peritoneal fluid. In the illustratedembodiment, this means sizing the beam at 1×-2× and, preferably, about1.5× the average size of the fluid components to be preferentially bedetected—here, WBCs. Given an average size of 12-15 μm for neutrophilsand eosinophils, 8-10 μm for lymphocytes, and 16-20 μm for monocytes,beam 52 of the illustrated embodiment is accordingly sized between 10-40μm and, preferably, 15-25 μm and, still more preferably, about 20 μm.This optimizes the apparatus 42 for preferential detection of WBCs over,for example, red blood cells 56, fibrin 58 and other components of theperitoneal fluid. Other embodiments may use other beam sizes, e.g., forreason of preferential detection of other peritoneal fluid components orotherwise.

As above, the beam 52 emanating from the bundle 102 of the illustratedembodiment is aimed to pass through the peritoneum 14 in order toilluminate peritoneal fluid therein for purposes of evoking scatteringfrom biological (and other) components in that fluid.

As above, illuminant scattered by peritoneal fluid in the peritoneum 14,e.g., in a direction normal to beam 52 is transmitted along the catheter19 to the detector 46 by fiber optic bundle 104. From that illuminant,detector 46 determines the index of refraction of the peritoneal fluid,in addition to detecting and counting of scattering events (i.e., eventsin which illuminant is scattered by fluid in the peritoneum 14 to thedistal end of bundle 104), based on the intensity and/or location ofthose events.

In the illustrated embodiment, the distal end of bundle 104 is arrangedto capture (and transmit to the detector 46 for detection)side-scattering, e.g., events within a field of view 64 centered on anaxis 66 that is normal to the beam 52, as shown. In other embodiments,the distal end of the bundle is arranged to capture (and transmit to thedetector for detection) other scattering events, e.g., back-scattering,forward-scattering, side-scattering at angles β other than normal. Thus,while in the illustrated embodiment, β is substantially 90°, moregenerally, β is in the range 30°-150°; more preferably, between,60°-120°; still more preferably, between 80°-100°; and, still morepreferably, substantially 90°, as illustrated.

As above, in some embodiments, the detector 46 employs a single-cell (orfew-celled) photo diode, i.e., pin-diode 68, for purposes of detectingand signaling the occurrence of such scattering events. A lens 70facilitates focusing the diode so that it detects those events at acellular scale of resolution, e.g., on a scale such that separatecellular-sized biological (or other) components in the peritoneal fluidcan be distinguished (based on such scattering) from one another. In theillustrated embodiment, lens 70 is selected and arranged (vis-a-vis theproximal end of bundle 104 and diode 68) to preferentially focus WBCs,though, in other embodiments, the lens 70 may be focused otherwise. Thelens 70 is further selected and arranged for a desired depth of focusvis-a-vis field of view 64, e.g., in the illustrated embodiment, a depthof focus from about a few centimeters to about a few inches.

As above, the laser diode 68 is selected and/or otherwise configured(e.g., through use of appropriate circuitry) to detect scattering fromselected components of the peritoneal fluid—here, preferentially, WBCs,though, in other embodiments, RBCs, fibrin, bubbles other components ofthe fluid. Regardless, such selection and/or configuration can beperformed empirically (e.g., by testing scattering detected from a fluidof known composition) or otherwise.

As above, other embodiments of the invention employ a charge-coupleddevice (CCD), in place of pin-diode 68; for purposes of detecting andsignaling the occurrence of scattering events. And, too, lens 70facilitates focusing the CCD (and obtaining a desired depth of focus) sothat it detects those events at a cellular scale of resolution and, inthe illustrated embodiment, so that it preferentially focusesWBCs—though, in other embodiments, the lens 70 may be focused otherwise.In the discussion that follows, elemental designation 68 is used for theCCD, as it was for the pin-diode, since the CCD is disposed in the samefunctional place in apparatus 100 a.

As with the pin-diode, the CCD 68 is selected and/or otherwiseconfigured to facilitate detection of scattering from selectedcomponents of the peritoneal fluid (again, here, preferentially, WBCs)and for determination of the index of refraction of the peritonealfluid. In this regard, the CCD 68 images the illuminated peritonealfluid (via fiber optic bundle 104), recording both the positions andintensities of scattering events (again, at a cellular scale ofresolution) so that at least selected components (e.g., WBCs) in theperitoneal fluid can be distinguished from one another and from othercomponents of that fluid.

As above, scattering events detected and signaled by the diode 60 arerouted to microprocessor 62 (or other suitable element) for analysis. Inthe illustrated embodiment, this comprises counting events signaled overtime and generating an alert, e.g., when the number of counts of acertain intensity (or range of intensities) varies, e.g., (i) from abaseline established for patient 16, (ii) among successive drains ofspent PD solution from that patient 16, and/or (iii) when a trend ofthat variance over time—and, more particularly, a rate of change ofcounts over time (i.e., a ‘critical slope’)—exceeds a selected amount.Such an alert can be in the form of a visible and/or audible signal tothe patient 16, health-care worker, or otherwise; a hardware or otherinterrupt to system 12 of which test apparatus 100 a forms a part; asoftware function call to such system; or otherwise. In addition, themicroprocessor determines the index of refraction of the fluid in theperitoneum 14 based on the intensity of the scattering events detectedby diode 60.

In the embodiment of FIGS. 7A-7B, such alerts and index of refractionmeasurements are transmitted from apparatus 100 b to a remote interfaceunit 100 b. Such transmission can be over a wireless or airedconnection, or a combination thereof. In the illustrated embodiment,wireless transmission is employed via module 106, which utilizes theBluetooth® wireless protocol to communicate (i.e., transmit and receiveinformation) with remote unit 100 b. Other embodiments may use infrared,802.11, or other wireless communication technologies (includinglong-distance wireless technologies, like satellite) instead or inaddition. Still others may utilize wired connections (such as USBcables, Ethernet, and so forth), in combination with or exclusive ofsuch wireless technologies.

Apparatus 100 b, which can be sized and configured to be slippedonto/into a pocket or “worn” by the patient 16, a health care provider,or otherwise, receives such alerts index of refraction measurements fordisplay on LCD or other display screen 108 and/or LEDs or otherindicators 110. To this end, the apparatus 100 b can employ amicroprocessor or other circuitry (not shown) for further analysis ofthe alerts and information from apparatus 100 a regarding scatteringevents, index of refraction measurements and other information (e.g.,regarding battery levels and/or other aspects of the operational statusof apparatus 100 a). Indeed, such a microprocessor or other circuitryresident in apparatus 100 b can provide some or all of the functionalityof microprocessor 62, thereby, reducing the circuitry requirements ofapparatus 100 a.

More generally, the microprocessor or other circuitry of resident inapparatus 100 b can control apparatus 100 a, e.g., activating detector46 and/or drive circuitry 108. To this end, apparatus 100 b provides akeyboard 112 for accepting input from the patient, health care provideror others for activating the unit, entering codes for pairing Bluetoothmodule 106 or otherwise coupling/decoupling apparatus 100 a and 100 bfor communications, specifying operational modes for detector 46 and/ordrive circuitry 108 (and, more generally, apparatus 100 a and 100 b),and/or otherwise.

The circuitry of apparatus 100 a and 100 b can be powered by batteries,such as by way of non-limiting example two flat “watch type” batteries(not shown), or otherwise. Furthermore, that circuity can be implementedusing surface mounted printed circuit board technology, or otherwise, inorder to conserve space. As such, apparatus 100 a of the illustratedembodiment is approximately 1.5″×1″×0.5″, though, the dimensions ofother embodiments may vary. Likewise, apparatus 100 b of the illustratedembodiment is approximately 3″×2″×1″, though, again, the dimensions ofother embodiments may vary.

Described and shown herein are apparatus and methods for testing PDeffluent meeting the objects set forth above. It will be appreciatedthat the embodiments described here are merely examples of the inventionand that other embodiments, incorporating changes therein, fall withinthe scope of the invention. Thus, by way of non-limiting example, itwill be appreciated that the apparatus and methods as described abovefor use in detecting peritonitis from PD effluent flow can be applied indetecting characteristics of dialysate and other fluids contained inand/or from other bodily organs and cavities in vivo, in vitro andotherwise, including detecting such conditions as blood (RBCs), bubblesand other desirable or undesirable byproducts of CAPD, APD and so forth,all by way of non-limiting example. Further, it will be appreciated thatsuch apparatus and methods can be applied in detecting bubbles and otherbyproducts of hemodialysis.

1. Apparatus for in vivo testing of fluids in a patient's body,comprising A. an illuminant source and illuminant detector, bothdisposed external to a patient, B. a first fiber optic bundle thatcarries illuminant from the source into the patient's body, C. a secondfiber optic bundle that carries illuminant scattered by fluid patient'sbody to the detector, D. wherein distal ends of the first and secondfiber optic bundles are configured so that the latter captures andtransmits to the detector reflected and/or scattered (collectively,“scattered”) illuminant at a cellular scale of resolution.
 2. Theapparatus of claim 1, wherein the first and second fiber optic bundlesare configured so that the latter captures and transmits to the detectorscattered illuminant on a scale such that separate cellular-sizedbiological or other components in the patient's body can bedistinguished from one another.
 3. The apparatus of claim 1, wherein anyof the first and second fiber optic bundles are routed to the patient'sbody via a catheter.
 4. The apparatus of claim 1, comprising any of alens and a columnator disposed at a proximal end of the first fiberoptic bundle to shape illuminant generated by the source for transfer tothe first fiber optic bundle.
 5. The apparatus of claim 1, comprisingany of a lens and a columnator disposed at a distal end of the firstfiber optic bundle to shape illuminant transmitted thereby into thepatient's body.
 6. The apparatus of claim 1, wherein illuminantemanating from the distal end of the first fiber optic bundle evokesscattering from biological and other components in the patient's body.7. The apparatus of claim 6, wherein a distal end of the second opticfiber bundle is arranged to capture and transmit to the detector suchscattered illuminant.
 8. The apparatus of claim 7, wherein the distalend of the second optic fiber bundle is arranged to capture illuminantside-scattered by biological and other components in the patient's body.9. The apparatus of claim 7, wherein the distal end of the second opticfiber bundle is arranged to capture illuminant any of back-scattered,forward-scattered, and/or side-scattered by biological and othercomponents in the patient's body.
 10. Apparatus for in vivo testing offluid in a bodily organ or cavity of a patient, comprising A. acatheter, B. an illuminant source and illuminant detector, both disposedexternal to a patient, C. a first fiber optic bundle that carriesilluminant from the source into the bodily organ or cavity, D. a secondfiber optic bundle that carries to the detector illuminant scattered byfluid, including biological or other components therein, contained inthe bodily organ or cavity, E. the first and second fiber optic bundlesbeing disposed at least partially in the catheter, F. a tip disposed ata distal end of the catheter for securing distal ends of the first andsecond fiber optic bundles such that the latter captures and transmitsto the detector illuminant reflected and/or scattered (collectively,“scattered”) in the bodily organ or cavity.
 11. The apparatus of claim10, wherein the first and second fiber optic bundles are configured sothat the latter detects and transmits to the detector scatteredilluminant on a scale such that separate cellular-sized biological orother components in the peritoneum can be distinguished from oneanother.
 12. The apparatus of claim 10, wherein the source is a laserdiode or other source of coherent illuminant.
 13. The apparatus of claim12, comprising any of A. a lens and a columnator disposed at a proximalend of the first fiber optic bundle to shape illuminant generated by thesource for transfer to the first fiber optic bundle, B. any of a lensand a columnator disposed at a distal end of the first fiber opticbundle to shape illuminant transmitted thereby into the patient's body.14. The apparatus of claim 10, comprising an interface unit that isdisposed remotely from the detector and that displays informationreceived therefrom.
 15. The apparatus of claim 14, wherein the remoteinterface is coupled with the detector by way of a wireless link. 16.The apparatus of claim 15, wherein the wireless link is any of aBluetooth and infrared link.
 17. The apparatus of claim 14, wherein theremote interface is coupled with the detector by way of any of a wiredlink, a wireless link or a combination thereof.
 18. The apparatus ofclaim 14, wherein the interface unit controls any of the detector andthe source.
 19. The apparatus of claim 14, wherein the remote interfaceis any of sized and configured to be slipped onto/into a pocket and/orworn by the patient, a health care provider, or other person. 20.Apparatus for in vivo testing of peritoneal fluid, comprising A. atleast one of a catheter and a transfer set, B. an illuminant source andilluminant detector, both disposed external to a patient, C. a firstfiber optic bundle that carries illuminant from the source into thepatient's peritoneum, D. a second fiber optic bundle that carries to thedetector illuminant scattered by fluid, including biological or othercomponents therein, contained in the peritoneum, E. the first and secondfiber optic bundles being disposed at least partially in the catheter,F. distal ends of the first and second fiber optic bundles beingdisposed in the peritoneum such that the latter captures and transmitsto the detector illuminant reflected and/or scattered (collectively,“scattered”) in the peritoneum.
 21. Apparatus according to claim 20, inwhich the detector is arranged to determine a refraction index of fluidin the peritoneum as a function of illuminant scattered by fluidtherein.
 22. Apparatus according to claim 20, in which the detector isarranged to detect illuminant scattered from separate white blood cells(WBCs) in the peritoneum such that those WBCs can be distinguished fromone another.
 23. Apparatus according to claim 22, wherein the detectorcounts WBCs in the peritoneum based on illuminant scattered therefrom.24. Apparatus according to claim 23, wherein the detector signals anonset of peritonitis if said counts change over time and/or vary from abaseline.
 25. Apparatus according to claim 24, wherein said baseline isa baseline previously established for the patient.
 26. Apparatusaccording to claim 20, in which the detector is arranged to detectilluminant scattered from cellular-sized components of different typesin the peritoneum such that those components can be distinguished fromone another.
 27. Apparatus according to claim 26, in which the detectoris arranged to detect illuminant scattered from white blood cells (BCs)in the peritoneum such that they can be distinguished from red bloodcells (RBCs), fibrin and/or other components from which illuminant isscattered in the peritoneum.
 28. Method for in vivo testing ofperitoneal fluid, comprising A. illuminating fluid in a patient'speritoneum, B. detecting illuminant any of reflected and scattered(collectively, “scattered”) by the fluid at a cellular scale ofresolution such that at least selected separate cellular-sizedcomponents in the fluid can be distinguished from one another based onilluminant that is scattered therefrom.
 29. Method according to claim28, comprising detecting illuminant scattered from separate white bloodcells (WBCs) in the peritoneum such that those WBCs can be distinguishedfrom one another.
 30. Method according to claim 29, comprising countingWBCs in the peritoneum based on illuminant scattered therefrom. 31.Method according to claim 30, comprising signaling an onset ofperitonitis if said counts change over time and/or vary from a baseline.32. Method according to claim 28, comprising detecting illuminantscattered from cellular-sized components of different types in theperitoneum such that those components can be distinguished from oneanother.
 33. Method according to claim 33, comprising detectingilluminant scattered from white blood cells (WBCs) in the effluent suchthat they can be distinguished from red blood cells (RBCs), fibrinand/or other components from which illuminant is scattered in thepertioneum.
 34. Method for testing fluid in any body cavity or organ,comprising A. illuminating fluid in the body cavity or organ, B.detecting illuminant any of reflected and scattered (collectively,“scattered”) by the fluid at a cellular scale of resolution such that atleast selected separate cellular-sized components in the fluid can bedistinguished from one another based on illuminant that is scatteredtherefrom.